There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Offering a unifying theoretical perspective not readily available in any other text, this innovative guide to econometrics uses simple geometrical arguments to develop students' intuitive understanding of basic and advanced topics, emphasizing throughout the practical applications of modern theory and nonlinear techniques of estimation. One theme of the text is the use of artificial regressions for estimation, reference, and specification testing of nonlinear models, including diagnostic tests for parameter constancy, serial correlation, heteroscedasticity, and other types of mis-specification. Explaining how estimates can be obtained and tests can be carried out, the authors go beyond a mere algebraic description to one that can be easily translated into the commands of a standard econometric software package. Covering an unprecedented range of problems with a consistent emphasis on those that arise in applied work, this accessible and coherent guide to the most vital topics in econometrics today is indispensable for advanced students of econometrics and students of statistics interested in regression and related topics. It will also suit practising econometricians who want to update their skills. Flexibly designed to accommodate a variety of course levels, it offers both complete coverage of the basic material and separate chapters on areas of specialized interest.

Estimation and Inference in Econometrics

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

The somatic genomic landscape of glioblastoma

It is important that the medical profession plays a significant role in critically evaluating the use of diagnostic procedures and therapies as they are introduced and tested in the detection, management, or prevention of disease states. Rigorous and expert analysis of the available data documenting absolute and relative benefits and risks of those procedures and therapies can produce helpful guidelines that improve the effectiveness of care, optimize patient outcomes, and favorably affect the overall cost of care by focusing resources on the most effective strategies.

The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of such guidelines in the area of cardiovascular disease since 1980. The ACC/AHA Task Force on Practice Guidelines, whose charge is to develop, update, or revise practice guidelines for important cardiovascular diseases and procedures, directs this effort. The Task Force is pleased to have this guideline developed in conjunction with the European Society of Cardiology (ESC). Writing committees are charged with the task of performing an assessment of the evidence and acting as an independent group of authors to develop or update written recommendations for clinical practice.

Experts in the subject under consideration have been selected from all 3 organizations to examine subject-specific data and write guidelines. The process includes additional representatives from other medical practitioner and specialty groups when appropriate. Writing committees are specifically charged to perform a formal literature review, weigh the strength of evidence for or against a particular treatment or procedure, and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that might influence the choice of particular tests or therapies are considered as well as frequency of follow-up and cost effectiveness. When available, information from studies on cost will be considered; however, review …

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ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines

15-year-old boy with ocular palsy and headache. Invasive macroprolactinoma.

While World Health Organization (WHO) grade 2, or atypical, meningiomas comprise approximately 25% of meningiomas, they represent the population with increased propensity for local recurrence and even decreased survival (1). Unfortunately, there are a paucity of prospective data to guide clinical management, as the largely retrospective studies on this disease are fraught with patient selection bias, insufficient follow-up, and small numbers of events. Unanswered clinical questions for grade 2 meningiomas include the role of adjuvant radiation therapy for gross totally resected tumors (2, 3) and the use of stereotactic radiosurgery given the higher local and marginal failure rate after stereotactic radiosurgery (4). Proton radiation therapy is also being explored, allowing for treatment of larger volumes more suitable for conventional fractionation but with decreased integral dose than photon therapy. The lack of effective systemic agents for the treatment of progressive or recurrent meningiomas represents an unmet clinical need. A population of patients with meningiomas will experience multiple recurrences and suffer from the cumulative toxicities of multiple sequential local therapies (1, 2, 4). For this population, treatment options are ultimately exhausted, and patients succumb to unrelenting meningioma. While past studies have yielded few options with even modest antitumor activity (5), present and future trials will use next-generation sequencing to triage patients to identify suitable clinical trials. WHO updated the definition of grade 2 meningiomas in both 2000 and 2007. The rationale for these changes was the limited ability of histology to predict biological behavior. In spite of the updates, serious limitations persist. Since the 2007 WHO update, there has been a growing interest in the molecular pathogenesis of meningiomas, particularly in the search for specific mutations that may be

Atypical Meningioma: An Evolving Landscape and Moving Target

Although surgical excision is the treatment of choice for accessible skull base meningiomas, a significant subset of complex tumours tightly attached to or encasing neurovascular structures cannot be removed safely via surgery alone. In patients with residual or progressing disease after incomplete tumour resection, adjuvant external beam radiation therapy (RT) has traditionally been employed, with a reported local tumour control rate of up to 90% at 10 years. In recent decades, RT has evolved to encompass conformal and stereotactic techniques. The dramatic technical advances in all aspects of treatment have led to better immobilization, imaging, planning, and treatment. Advanced radio-oncology techniques include intensity-modulated radiotherapy (IMRT), volumetric arc therapy (VMAT), and stereotactic radiotherapy (SRT) and radiosurgery (SRS), which allow for more precise dose delivery to the tumour while limiting the amount of radiation to the sensitive brain structures, i.e. the optic pathway and the brainstem. New radiation techniques, particularly SRS, have progressively emerged as effective primary treatments for selected meningiomas of the skull base. Large series demonstrate local control rates of over 90% at 5 years following SRS, and above 80% at 10–15 years. Although virtually non-invasive, SRS carries a risk of late radiation-induced toxicity, typically cranial nerve deficits causing impaired visual acuity and ocular motility. For patients with large skull base meningiomas or tumours in close proximity to the optic pathway, fractionated SRS (2–5 fractions) has emerged as an alternative to single-fraction SRS, with the hope of reducing the long-term consequences of treatment while maintaining its effectiveness. Currently, SRT and SRS are an essential part of the modern management of skull base meningiomas recurring after surgery or in difficult-to-access locations.

Single- Versus Multiple-Fraction Stereotactic Radiotherapy

Automated treatment planning systems are available for linear accelerator (linac)-based single-isocenter multi-target (SIMT) stereotactic radiosurgery (SRS) of brain metastases. In this study, we compared plan quality between Brainlab Elements Multiple Brain Metastases (Elements MBM) software which utilizes dynamic conformal arc therapy (DCAT) and Varian HyperArc (HA) software using a volumetric modulated arc therapy (VMAT) technique.Between July 2018 and April 2021, 36 consecutive patients ≥ 18 years old with 367 metastases who received SIMT SRS at UPMC Hillman Cancer San Pietro Hospital, Rome, were retrospectively evaluated. SRS plans were created using the commercial software Elements MBM SRS (Version 1.5 and 2.0). Median cumulative gross tumor volume (GTV) and planning tumor volume (PTV) were 1.33 cm3 and 3.42 cm3, respectively. All patients were replanned using HA automated software. Extracted dosimetric parameters included mean dose (Dmean) to the healthy brain, volumes of the healthy brain receiving more than 5, 8,10, and 12 Gy (V5Gy, V8Gy, V10Gy and V12Gy), and doses to hippocampi.Both techniques resulted in high-quality treatment plans, although Element MBM DCAT plans performed significantly better than HA VMAT plans, especially in cases of more than 10 lesions). Median V12Gy was 13.6 (range, 1.87-45.9) cm3 for DCAT plans and 18.5 (2.2-62,3) cm3 for VMAT plans (p < 0.0001), respectively. Similarly, V10Gy, V8Gy, V5Gy (p < 0.0001) and median dose to the normal brain (p = 0.0001) were favorable for DCAT plans.Both Elements MBM and HA systems were able to generate high-quality plans in patients with up to 25 brain metastases. DCAT plans performed better in terms of normal brain sparing, especially in patients with more than ten lesions and limited total tumor volume. 

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Single-isocenter multiple-target stereotactic radiosurgery for multiple brain metastases: dosimetric evaluation of two automated treatment planning systems

Abstract Purpose Amino acid PET is a useful complement to MRI in a number of clinical settings for the evaluation of brain tumors. However, amino acid PET is rarely used repeatedly over the course of the disease. We reviewed the existing literature on the use of repeated amino acid PET imaging for monitoring primary or secondary brain tumors. Methods A comprehensive literature search of articles describing the use of longitudinal amino acid PET imaging of brain tumors was performed on PubMed/MEDLINE using multiple search terms. Additional literature was retrieved from the reference lists of identified studies or based on the authors’ personal knowledge and experience. Results With regard to primary tumors, two main clinical settings were identified in whom the performance of repeated amino acid PET imaging was most commonly assessed. These include the detection of malignant progression of patients with grade II or III glioma characterized according to older WHO classifications, and the early response assessment of various treatment options in glioma patients. For patients with brain metastases, only a few studies were identified using longitudinal amino acid PET for the diagnosis of post-treatment changes after stereotactic radiosurgery. The analyzed studies reported that longitudinal amino acid PET imaging frequently anticipate or even outperform the diagnostic performance provided by conventional MRI in these settings. Conclusions The available literature suggests that conventional MRI should be accompanied by longitudinal amino acid PET monitoring in these clinical settings. Nevertheless, more reliable evidence derived from larger, prospective multicenter studies is warranted. 

https://link.springer.com/content/pdf/10.1007/s40336-023-00555-7.pdf

Giuseppe Minniti

Papers

15-year-old boy with ocular palsy and headache. Invasive macroprolactinoma.

Atypical Meningioma: An Evolving Landscape and Moving Target

Single- Versus Multiple-Fraction Stereotactic Radiotherapy

Single-isocenter multiple-target stereotactic radiosurgery for multiple brain metastases: dosimetric evaluation of two automated treatment planning systems

Correction to: Repeated amino acid PET imaging for longitudinal monitoring of brain tumors